CD40L inhibits cell growth of THP-1 cells by suppressing the PI3K/Akt pathway

Abstract

Zhongxin Feng,1,2,* Qi Chen,2,* Mingqiang Ren,2 Zuguo Tian,2 Yuping Gong1 1Department of Hematology, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, China; 2Department of Hematology, Affiliated Hospital of Zunyi Medical University, Zunyi, China *These authors contributed equally to this work Introduction: Acute myeloid leukemia (AML), the hematological malignant tumor with high mortality, is still difficult to treat. CD40L is a type II transmembrane protein, which has been reported to have the potential to inhibit growth of some cancer cells. Materials and methods: In order to determine the role of CD40L on AML-M5 cell line THP-1, we overexpressed CD40L in the cells using a lentiviral vector system (pHBLV-CMVIE-Zs Green-T2A-puro vector); overexpression was confirmed by the detection of green fluorescent protein and CD40L protein expression. Results: Cellular apoptosis, proliferation, and cycle assays showed that CD40L could promote the apoptosis of, suppress the proliferation of, and stimulate the arrest of the G1/S phase of THP-1 cells. Finally, the protein expression of P53, Bax/Bcl-2, cyclinD1, PCNA, PTEN, and p-Akt illustrated that CD40L may partly influence cell growth of THP-1 cells through those genes, which was confirmed by immunohistochemistry and a PI3K/Akt activator. Conclusion: Taken together, CD40L could inhibit cell growth of THP-1 cells through the PI3K/Akt pathway, indicating that the overexpression of CD40L may be a potential target to treat the AML-M5 disease. Keywords: CD40L, cell proliferation, AML-M5, P53, cyclinD1, PCNA, tumor suppressor, cell apoptosis

Keywords

• CD40L
• cell proliferation
• AML-M5
• P53
• cyclinD1
• PCNA